Most periodontal diseases are considered to be a kind of infectious disease caused by indigenous microbes residing in the periodontal area. Among such indigenous microbes, a gram-negative anaerobic bacterium called Porphyromonas gingivalis (hereinafter abbreviated as “P. gingivalis”) has been revealed to be the most important pathogenic bacterium that causes adult periodontitis and rapidly progressive periodontitis (J. Clin. Periodontol., 15, 85–93, 1988; ibid 316–323, 1988; J. Dent. Res., 63, 441–451, 1984). In recent years, it has become known that proteases produced by P. gingivalis decompose periodontal tissue components such as collagen and blood serum proteins involved in the body's natural defense system and the proteases have revealed to be closely related to the pathogenicity of P. gingivalis (Greiner D., Mayrand D.: Biology of the Species Porphyromonas Gingivalis, Edited by Shah H. N., Mayrrand D. and Genco R. J., pp. 227–243, CRC Press, Boca Raton, Ann Arbor, London, Tokyo, 1993).
Several kinds of proteolytic enzymes having trypsin-like protease activity and produced by P. gingivalis are known. Among them, Lys-gingipain (hereinafter sometimes abbreviated as “KGP”) and Arg-gingipain (hereinafter sometimes abbreviated as “RGP”) are the principal proteolytic enzymes. These enzymes are known to have potent digestive activities to decompose high molecular weight kininogen and fibrinogen and are considered to be involved in bacterial attachment, the onset of periodontal disease and periodontal tissue destruction (J. Biol. Chem., 269, 406–411, 1994).
Conventionally, drugs for inhibiting the growth of bacteria are used to prevent and treat periodontal disease. Examples of such drugs include antibiotics such as tetracycline and minocycline; natural products such as chamomile tincture and rhatany tincture; cyclohexadine, tranexamic acid and the like. However, these drugs have safety problems or other various problems such as unpleasant smell. Japanese Unexamined Patent Publication No. 1993-97708 discloses periodontal therapeutic agents comprising an ATPase inhibitor, a cysteine protease inhibitor or the like as an active ingredient. Japanese Unexamined Patent Publications Nos. 1999-139947 and 2000-191487 disclose a composition for use in the oral cavity comprising a matrix metalloprotease inhibitor as an active ingredient. However, the anti-periodontal disease effects of the therapeutic agent and the composition are not satisfactory. Recently known inhibitors for selectively inhibiting RGP are malabaricon C described in Japanese Unexamined Patent Publication No. 1999-335274 and an arginine derivative described in Japanese Unexamined Patent Publication No. 1999-228526. A lysine derivative described in Tissue Culture Engineering, 27 (9), 343–347, 2001 is known as an inhibitor capable of selectively inhibiting KGP.
However, these publications do not describe a compound capable of inhibiting both enzymes, KGP and RGP.